The present disclosure relates to processes and apparatuses for producing high-loading, biologically active microparticles under ambient conditions, as well as the microparticles produced thereby. Such microparticles are useful in many fields, including drug delivery, for delivering proteins, peptides, and other bioactive molecules.
The production of protein microparticles for the purpose of stabilization or to provide a convenient vehicle for an intended application has been the subject of much investigation in recent years. Traditional methods for producing protein microparticles include controlled precipitation, milling of lyophilized protein product, microemulsion techniques, and spray drying, which is perhaps the most widely employed method. Each traditional method is limited in its capacity to control particle design features (e.g. size, dispersity, morphology, density) and most impart processing stresses that can lead to protein destabilization. For example, the standard approaches of spray drying and freeze drying impart considerable biological activity losses due to thermal, interfacial, and shear stress. Maintenance of biological activity and control of particle physical features during formation is critical in many fields of use, including but not limited to drug delivery. Process stress is typically mitigated by the addition of excess equivalents of stabilizing excipients (e.g. polyols, surfactants), which results in low microparticle biological density and creates an opportunity for off-target effects due to the added excipients. It would be desirable to be able to produce biologically-active, protein-rich microparticles for maximizing biological payload in fixed volume operations, such as drug delivery by injection.